The recently released ICH E14/S7B 2022 Q&As provides the best practice guidelines for evaluating the effect of preclinical compounds on the human ether-à-go-go-related gene (hERG) potassium channel1. The guidelines stipulate that in vitro hERG assessments should be performed to GLP compliance. In addition, it provides recommendations on the experimental methods that should be employed, the quality control parameters for analysing the data, as well as the preferred format for reporting the data. This is to ensure data quality, transparency and consistency throughout the industry. A hERG assay is considered negative if the safety margin calculated for the test article is greater than the established safety margins generated with the FDA’s positive controls (ondansetron, moxifloxacin and dofetilide) tested to the best practice guidelines. Metrion conducted a GLP compliant study using the conventional manual patch-clamp technique in accordance with the ICH E14/S7B Q&A best practice guidelines to establish in-house IC50 values for ondansetron, moxifloxacin and dofetilide.
The HESI Cardiac Safety Committee present results from an international ion channel research study that assessed the variability of hERG data generated using automated patch clamp platforms (QPatch 48, Qube 384 and the SyncroPatch 384i) across four different labs.
We developed a high-throughput, electrophysiological assay of TREK-1 function to identify novel modulators. The assay was optimized to identify both activators and inhibitors, providing comprehensive mechanistic data for high value, limited supply screening libraries, such as the venom fraction library used in this study (Targeted Venom Discovery Array, T-VDA, Venomtech, UK).